incidence of pancreatitis and pancreatic cancer in a randomized controlled multicenter trial...

Incidence of Pancreatitis and Pancreatic Cancer in a Randomized Controlled

Multicenter Trial (SAVOR-TIMI 53) of the Dipeptidyl Peptidase-4 Inhibitor Saxagliptin

Featured Article:

Itamar Raz, Deepak L. Bhatt, Boaz Hirshberg, Ofri Mosenzon, Benjamin M. Scirica, Amarachi Umez-Eronini, KyungAh Im, Christina Stahre, Alona

Buskila, Nayyar Iqbal, Norton Greenberger, and Markus M. Lerch

Diabetes Care Volume 37: 2435-2441

September, 2014

STUDY OBJECTIVE 

• To determine the incidence of pancreatitis and pancreatic cancer in the SAVORTIMI 53 trial

Raz I. et al. Diabetes Care 2014;37:2435-2441

STUDY DESIGN AND METHODS

• 16,492 type 2 diabetic patients ≥40 years old with cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo

• Patients were followed for 2.1 years

• Outcome measures were investigator-reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer

Raz I. et al. Diabetes Care 2014;37:2435-2441

RESULTS

• Trial investigators reported 35 events of pancreatitis in each treatment arm in 63 patients

• Adjudication confirmed pancreatitis in 24 patients (26 events) in the saxagliptin arm and 21 patients (25 events) in the placebo arm

• Cases of definite acute pancreatitis were confirmed in 17 vs. 9, definite plus possible pancreatitis in 22 vs. 16, and chronic pancreatitis in 2 vs. 6 in the saxagliptin and placebo arms, respectively

Raz I. et al. Diabetes Care 2014;37:2435-2441

RESULTS

• No differences were found between treatment arms in the following:

• Time to event onset• Concomitant risk factors for pancreatitis• Investigator-reported causality from study medication or

disease severity• Outcome

• The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively

Raz I. et al. Diabetes Care 2014;37:2435-2441

Raz I. et al. Diabetes Care 2014;37:2435-2441

Raz I. et al. Diabetes Care 2014;37:2435-2441

Raz I. et al. Diabetes Care 2014;37:2435-2441

CONCLUSIONS

• Risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and apparently similar to placebo

• There was no sign of increased risk for pancreatic cancer

• Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy

Raz I. et al. Diabetes Care 2014;37:2435-2441